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Alzheimer’s disease and other tau-related disorders are often viewed primarily as neuronal diseases, yet brain connectivity also depends on oligodendrocytes and myelin, the lipid-rich insulation surrounding nerve fibers. How glial metabolism, myelin, and adenosine balance influence brain connectivity remains unclear. Researchers led by Dr. Yijuang Chern of the Institute of Biomedical Sciences at Academia Sinica and Dr. You-Yin Chen of National Yang Ming Chiao Tung University integrated data from brain tissue, diffusion MRI, and multi-omics to investigate these relationships through ENT1, a key regulator of adenosine transport. The study links myelin abnormalities to impaired hippocampal-prefrontal connectivity in tauopathy. Inhibiting ENT1 by J4 improved myelin organization and brain connectivity while reshaping purine and lipid metabolism associated with myelin-forming oligodendrocytes. These findings identify ENT1 as a potential therapeutic target for restoring brain network function in Alzheimer’s disease and related tauopathies. The study was published on September 11, 2026, in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association (Impact Factor 12.8).